tbuckley/cabot-search huggingface dataset:
LGG-31. Pediatric low-grade gliomas with FGFR1 mutations and spontaneous hemorrhage: case series
Authors: Stephani Campion, Ana E Aguilar-Bonilla, Samer Elbabaa, Amy A Smith
Journal: Neuro-Oncology (2022)

Abstract Pediatric low-grade gliomas (pLGG) are the most common pediatric CNS neoplasms. Thanks to the advent of molecular tumor diagnostics, we have begun exploring the clinical relevance of FGFR1 (c.1632C&amp;gt;A; p.N546K) mutations in the pLGG population. However, the risk of spontaneous hemorrhage in pLGG patients harboring FGFR1 mutations is even less understood. We present four pLGG cases with FGFR1 mutation and hemorrhagic episodes. Patient 1 presented with an intraventricular hemorrhage and leptomeningeal disease. Pathology was consistent with suprasellar pilocytic astrocytoma, FGFR1, and PTPN11 mutations. Initial therapy consisted of Carboplatin/Vinblastine per ADVL0515. The patient has had several recurrences, and treatment regimens have included ACNS0223, Everolimus, and A9952 regimen A. Patient 2 was diagnosed with an optic pathway glioma, and pathology confirmed FGFR1, MEK2, PTPN11, and NF1 splice site mutations. The patient also has a history of Noonan’s Syndrome and has undergone several chemotherapy regimens, including A9952 Regimen A, COG MATCH with Erdafitinib, and Avastin. The best tumor response was seen while on Avastin. The patient has presented with two episodes of intratumoral hemorrhage, both after treatment with Avastin. Patient 3 presented with a sudden brain stem hemorrhage and underwent a biopsy and debulking. The pathology was consistent with a pilocytic astrocytoma with an FGFR1 mutation confirmed by Next-generation sequencing (NGS). Treatment regimens for this patient include A9952 Regimen A and Vinblastine. Patient 4 presented with acute headache and vomiting and was found to have a hemorrhagic suprasellar mass. The patient underwent tumor debulking, and pathology was consistent with low-grade glioma. NGS revealed FGFR1 and KRAS mutations. The patient received therapy as per A9952 Regimen A. Greater surveillance of this molecular and clinical finding is warranted to uncover the association between FGFR1 mutations and hemorrhage in patients with low-grade gliomas.
CCND1 and PTEN gene copy number variations as markers of vulvar cancer progression.
Authors: Natalia A. Petrusenko, Denis S. Kutilin, Angelina V. Busarova, Natalya V. Porkhanova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e17531 Background: More than 90% of malignant vulvar tumors and almost 5% of all gynecological cancers are squamous cell carcinoma. 1/3 of patients with vulvar cancer relapse after initial treatment, and the 2-year overall survival is less than 15%. Development of more effective treatments requires understanding of the molecular pathogenesis of vulvar cancer. The aim of this study was the screening of potential prognostic tumor markers in vulvar cancer based on relative copy number analysis (CNV) of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C genes. Methods: The study was performed on 300 patients aged 29-80 years diagnosed with vulvar squamous cell carcinoma with lymph nodes metastases (n = 150) and without metastases (n = 150). The material for the study was DNA from FFPE-blocks of tumor and non-tumor vulvar tissues. The RT-qPCR method was used to evaluate the relative copy number of MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, AEPX1, NFKBIA, MTAP, BIRC2, SYNE1, KMT2C, GAPDH and B2M genes (the last two were reference genes). Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: All genes showed a change in the dose in vulva tumor cells relative to normal ones: amplifications for the MYC, MCL1, AEPX1, NFKBIA, CCND1, PIK3CA, TP53, MDM2, BIRC2, SYNE1, KMT2C genes, respectively, in 46%, 36%, 28%, 40%, 56%, 43%, 62%, 39%, 57%, 35%, 44% of cases, and a decrease in copy number for PTEN, MTAP, CDKN2A genes, respectively, in 34%, 28%, 35% of cases. At the same time, a statistically significant increase in the CNV of the CCND1 gene (p &lt; 0.05) by 1.7 times and a decrease in the PTEN gene (p &lt; 0.05) by 1.9 times were observed in the group of vulvar squamous cell carcinoma patients with lymph nodes metastases. No statistically significant change in the CNV of other genes was found. Conclusions: Thus, the identified aberrant copy numbers of CCND1 and PTEN genes can serve as prognostic markers for vulvar cancer patients.
Serum total cell-free DNA as a marker for invasive evaluation in total cystectomy
Authors: T. Narita, S. Konishi, S. Hatakeyama, T. Yoneyama, M.S. Yoneyama, Y. Tobisawa, D. Noro, T. Sato, K. Togashi, T. Okamoto, H. Yamamoto, T. Yoneyama, Y. Hashimoto, C. Ohyama
Journal: European Urology (2022)
Automated assessment of illness and treatment understanding (ITU) via the Memorial Sloan Kettering Patient Portal.
Authors: Andrew S. Epstein, Camila Bernal, Danielle R. Romano, Jessica Goldberg, Anjali V. Desai, Judith Eve Nelson
Journal: Journal of Clinical Oncology (2022)

e24146 Background: Patient-reported outcome (PRO) technology offers opportunities to address research questions and unmet clinical needs of cancer patients’ ITU. We tested the feasibility of PRO assessment of ITU. Methods: With the same 5-item questionnaire (2 open- [about expectations of cancer outcome and treatment intent] and 3 validated [Weeks JC NEJM 2012] closed-ended items) administered by medical oncology nurses in clinic in a previous pilot (Shin P ASCO 2020), we used the electronic patient portal in our cancer center to elicit responses from all gastrointestinal medical oncology patients scheduled for clinic follow-up. Patients registered on the portal received this questionnaire automatically the day before the second follow-up visit and then quarterly, with a brief explanation that it applied to all patients for quality improvement. Responses were available for review in the electronic health record by all oncology team members, who were offered a 20-minute Zoom introduction to this initiative. Workflow and content of communications about prognosis, treatment intent, and goals of care stayed within clinicians’ discretion. Results: From 5/2021 through 12/2021, 5000 questionnaires were sent to 3852 patients (1-3 times per patient, quarterly), of which all but one was returned, including 3863 with open- and closed-ended responses and 1135 with closed answers only. Patients: 55% male, 83% white, median age 64 (range, 15-96). Most common cancers: colorectal (54%) and pancreatic (21%). In patients with stage data (78%), 35% had stage IV disease. In closed-ended responses, patients receiving treatment (n = 2637 questionnaires) reported that based on the most recent discussions with the oncology team, they thought the treatment was at least a little likely to cure the cancer (66%), prolong life (98%), and/or help with cancer-related problems (92%). Open-ended answers ranged in length from 0-1013 words (median, 6; IQR, 10). Conclusions: Almost all patients in this large, heterogeneous cancer center cohort participated in an automatic assessment system via electronic patient portal addressing questions about their understanding of prognosis and treatment goals. PROs, traditionally focused on symptoms, represent a promising mechanism for scaling structured assessment of patients’ understanding of the prognosis and intent of their treatment. Our future research will address: effects in other cancer types/care settings; temporal changes in sequential responses: associations with clinical factors (e.g., stage, symptoms, treatment, oncologist documentation of prognosis/treatment intent, healthcare delivery and outcomes including patient reports of the quality of clinician communication); open vs. closed-ended questions for assessing ITU; administration in-person vs. via portal; and perspectives of patients and clinicians on our assessment process.
Unusual prevalence of cancer genetic mutations in a cohort of predominantly non-Caucasian cancer patients.
Authors: Nay Yee Wint Kyaw, Vijaya Natarajan, Theresa Durana, Pooja Gogia Bhasin, Jacob Best, Sudhamshi Toom, Yiqing Xu
Journal: Journal of Clinical Oncology (2022)

e22524 Background: Genetic testing has been applied increasingly widely in oncology, as detection of hereditary cancer syndromes can guide prophylactic surgery, intensive surveillance and family member testing. We hypothesized that the profile of mutation prevalence may be different from the general knowledge in patients with immigrant background. Methods: Cancer patients who have been treated in Maimonides hospital and have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Patients were randomly approached for consenting for the study. The results from the first 122 patients enrolled in this study were analyzed. Results: Among 122 patients, there were 86 breast, 22 GYN, 8 GI, 5 GU and 1 lung cancer. The ethnicities were African American (n = 38), Asian (n = 36), Caucasian (n = 32), Hispanic (n = 10) and mixed races (n = 6). Six patients had 2 primary cancers and 2 patients had 3 primary cancers. 25 patients (20.49 %) had germline mutations. A complete list of cancer type, mutation type, age of onset and cancer characteristics is shown in the table below. All of the 13 mutation positive breast cancer patients met the NCCN criteria for genetic testing, including 7 for age &lt; 50 and 6 with family history of breast cancer. Among the 2 patients with NF1 mutation, one had no skin change while the other had neurofibromatosis; both had family history, with pancreatic or breast cancer respectively. The patient with APC mutation had family history of numerous cancers including gastric, but no colon cancer. 48% patients had the onset of disease at older than 50 years old. Conclusions: In this multi-ethnicity cohort, 20.49% mutations were detected in patients who met the genetic testing criteria. A higher prevalence of BRCA 2 were found in both breast and ovarian cancer patients, and rare mutations of NF1, APC, FH and ATM were also detected. A large percentage had onset at an older age. More studies should be done in communities enriched with immigrants to gather further knowledge of unusual prevalence of genetic mutations, and an extensive panel for gene testing should be offered.[Table: see text]
Results of a phase 1b study of osimertinib plus sapanisertib or alisertib for osimertinib-resistant, EGFR-mutant non–small cell lung cancer (NSCLC).
Authors: Yasir Y Elamin, Marcelo Vailati Negrao, Frank V. Fossella, Lauren Averett Byers, Jianjun Zhang, Carl Michael Gay, Janet Chen Tu, Jenny Vu Pozadzides, Hai T. Tran, Charles Lu, Lei Feng, Amy R. Spelman, George R. Blumenschein, Anne S. Tsao, John Heymach
Journal: Journal of Clinical Oncology (2022)

9105 Background: The aurora kinase and mTOR pathways are implicated in resistance to EGFR inhibitor osimertinib. Here, we investigated the safety and efficacy of the aurora kinase inhibitor alisertib and the mTOR inhibitor sapanisertib in combination with osimertinib. Methods: This is a phase 1b study with dose finding and expansion portions (NCT04479306). The dose finding portion used a Bayesian optimal interval (BOIN) design to assess two arms: osimertinib 80 mg daily in combination with alisertib 20 mg, 30 mg, and 40 mg daily day 1-21 of 28-day cycle (osi-ali arm) and osimertinib 80 mg daily in combination with sapanisertib 2 mg and 3 mg daily (osi-sapa arm). Dose limiting toxicities (DLTs) were predefined in the protocol. Patients with EGFR (L858R/exon 19 deletion) mutant NSCLC whose disease have progressed on osi and up to one additional line of systemic therapy were assigned, at investigator discretion, to either study arm. Tumor biopsy was mandatory at study entry and optional upon progression. Results: As of February 1, 2022, 40 patients are enrolled (20 in each arm). One DLT was observed in each arm: grade 3 nausea in ali-osi arm and grade 3 AST elevation in osi-sapa arm. Grade 3 treatment emergent adverse events (TEAEs) occurred in 10% of each arm, and no grade 4 TEAEs were observed. The most common TEAEs in osi-ali arm was leucopenia (45%) and anemia (35%) while in osi-sapa arm, hyperglycemia (45%) and stomatitis (40%). In osi-ali arm (n = 20), median progression free survival (mPFS) was 1.9 months while objective response rate (ORR) and disease control rate (DCR) were 5% (95% CI: 0.1 ̃ 24.9%) and 40% (95% CI: 19.1 ̃ 63.9%), respectively. In osi-sapa arm (n = 16, evaluated for response to date), mPFS was 4.6 months while ORR and DCR were 12.5% (95% CI: 1.6 ̃ 38.3%) and 68.7% (95% CI: 35.7 ̃ 82.7%), respectively. Conclusions: Osimertinib with alisertib or sapanisertib is well tolerated in osimertinib-resistant, EGFR mutant NSCLC. The sapanisertib combination, but not the alisertib combination, demonstrates antitumor activity suggesting that mTOR inhibition warrants further exploration in this population. Biomarker analysis is ongoing to identify the molecular determinants of response and resistance to sapasertib. Clinical trial information: NCT04479306.
Liver-Directed and Systemic Therapy Options for Hepatocellular Carcinoma
Authors: Rajiv Agarwal, Lea K. Matsuoka, Daniel B. Brown
Journal: Journal of the National Comprehensive Cancer Network (2022)

Abstract Liver transplant and resection are preferable for the management of hepatocellular carcinoma, but ultimately, tumor location, biology, and patient condition dictate treatment decisions. At the NCCN 2022 Annual Conference, a panel of experts used 3 case studies to develop an evidence-based approach to the treatment of similar patients with hepatocellular carcinoma. Moderated by Daniel B. Brown, MD, FSIR, the session focused on current research regarding liver-directed and systemic therapy options.
Low lymphocyte counts and association with clinical outcomes in hospitalized patients with cancer receiving immune checkpoint inhibitor therapy.
Authors: Richard Young, Hemali Panchal, Weijie Ma, Shuai Chen, Aaron Paul Steele, Andrea A. Iannucci, Tianhong Li
Journal: Journal of Clinical Oncology (2022)

e14600 Background: Immune checkpoint inhibitors (ICIs) improve survivals in a variety of cancer patients by harnessing the immune system. Pre-treatment lymphopenia as measured by absolute lymphocyte counts (ALC) was associated with decreased progression-free survival (PFS) and overall survival (OS) in patients receiving ICIs. During hospitalization ICI treatment is often deferred and efficacy in this population is unclear. Our study explores outcomes and predictive factors for hospitalized patients who received ICI therapy. Methods: Cancer patients who received inpatient ICI were identified in the institutional pharmacy database from 08/2016 to 07/2021. Data were abstracted from electronic medical records. Data were summarized according to frequency and percentage for qualitative variables, and by mean ± standard deviation, median, and range for quantitative variables. The 95% confidence interval for survival was calculated using the exact binomial distribution. PFS and OS were estimated using the Kaplan–Meier method and compared using the log-rank test between groups. Receiver-operating characteristic (ROC) analysis was used to evaluate the discrimination ability of ALC for prognosis. Statistical significance was defined as 2-sided P &lt; 0.05. Results: Of 37 identified patients, 2 were excluded from the ALC analysis due to lack of blood counts. The most common cancer type treated was lung cancer (13, 35.1%). The majority of subjects were men (29, 78.4%) and the median age was 57 (21-79) years. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days, and the most common reasons for admission were initiation of therapy (14, 37.8%) and infection (5, 13.5%). Reasons for inpatient treatment included convenience (6, 16.2%), disposition delays (6, 16.2%), initiation of therapy (13, 35.1%), and emergent or last resort measures (10, 27.0%). Most patients died during the study period, and 5 were alive at the time of data analysis. 10 patients died during the same hospitalization as treatment. Of those who followed up, 22 died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Pre-treatment ALC &lt; 600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; HR 6.9, 95% CI 10.8-25.9, P = 0.0053) and poor OS (0.33 vs. 2.34 months; HR 4.66, 95% CI 1.2-17.5, P = 0.0236), respectively. Furthermore, patients with ALC &lt; 600 were less likely to receive a subsequent ICI dose than their counterparts. Conclusions: Administration of inpatient ICI therapy is associated with poor clinical outcomes and high rates of both inpatient mortality and death within 3 months of discharge. The presence of ALC &lt; 600/µL in hospitalized patients was associated with poor clinical outcomes.
Development of key performance indicator (KPI) for real-time monitoring of treatment of early breast cancer to control socioeconomic and indigenous systemic bias.
Authors: Euan Thomas Walpole, Philippa Youl, Danica Cossio, Michelle Frances Morris, Shoni Philpot
Journal: Journal of Clinical Oncology (2022)

10566 Background: Disparity in outcome for different cancer groups exist particularly for indigenous and poor socioeconomic background. Patient and treatment data on a population basis was examined. Methods: Population data for the state of Queensland, Australia (population 5.2M) collected by Cancer Alliance Queensland as part of government cancer registry roles plus additional linked data available as a gazetted quality assurance committee was examined to find patients with early breast cancer treated with surgery, chemotherapy (CT) and radiotherapy (RT) between 2005-2015. Results: A cohort of 8279 women received treatment with 89.3% having the surgery, CT, RT sequence. Time to completement threshold was 37 weeks using empirical cutpoint estimation in Stata. Overall survival (OS) was 94% at 5 years if &lt; 37 weeks versus 88.5% if not. (p &lt; 0.001). Multivariate analysis of socioeconomic and clinical characteristics for survival was also significant for increasing age, indigenous status, socioeconomic disadvantage, multiple co morbidities and advancing disease stage. Private hospital cases had a better outcome. When delay is analysed between treatments, only time to CT from surgery &gt; 9.5 weeks was significant for OS (HR 1.42 p &lt; 0.001). Indigenous status, socioeconomic status and private facility no longer were significant. Multiple co morbidities and advanced stage were still significantly associated with poorer survival. Funnel plots of treatment centre show the association with public hospital treatment and lower volume centre with delay. Conclusions: This data is retrospective so can inform local service evaluation but implementation of a KPI for delay to adjuvant chemotherapy of 9.5 weeks can provide real time targets for patient care. We measured delay in the recent 5 years (before survival available) which shows consistent delays and it will included as a reporting function of MDT management software. Whilst the increased use of neoadjuvant CT will assist, systematic reporting of this KPI has potential to remove treatment biases for indigenous and lower socioeconomic patients. More recent data will be available for presentation.
Comparison of predicted benefit using RS clin versus observed benefit in a U.S. registry of stage I ER-positive HER2-negative high oncotype DX RS breast cancer.
Authors: Christopher David Walden, Samuel Mosiman, Andrew J. Borgert, Benjamin Marshall Parsons
Journal: Journal of Clinical Oncology (2022)

544 Background: The 21-gene recurrence score assesses the risk of distant breast cancer recurrence and predicts the benefit of adjuvant chemotherapy in ER positive early-stage breast cancer. However, clinicopathologic risk factors continue to impact absolute benefit of adjuvant chemotherapy. Absolute benefit of adjuvant chemotherapy in low clinicopathologic risk Stage I ER positive breast cancer with high Oncotype RS is an important clinical component of shared decision making. The RSClin clinical tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was found to be more prognostic than RS result alone. We assessed RS Clin predicted benefit and compared to absolute benefit in low clinicopathologic risk Stage I ER positive breast cancer with high Oncotype RS as observed in the NCDB. Methods: Using the National Cancer Data Base (NCDB), we identified female patients age 18-75, ER positive and Her 2 negative, 21 gene signature high risk &gt; 25 with negatives surgical margins, &lt;2cm, lymph node negative breast cancers, who had received endocrine therapy with either Tam or AI diagnosed during 2010 - 2017. Clinicopathologic factors and RS were entered into the RSClin calculator, and a predicted benefit of chemotherapy was calculated for each patient. Using NCDB data, Cox proportional hazards regression models were used to project absolute survival benefit at 10 years from diagnosis for those who did vs those who did not receive chemotherapy. NCDB-derived absolute benefit of chemotherapy was compared to estimated absolute benefit as predicted by the RSClin tool. Results: 18,226 patients were identified. Stages T1a = 670(4%), T1b = 4,289(23%), and T1c = 13,267(73%). Median age 59 years (21-75). Race white 84% (15,365), black 10% (1840), and other 1021(6%). AI use 80% (14,711) was greater than Tam use 20% (3515). Chemotherapy was administered in 75% (13,827) of patients. Most patients had high or intermediate grade disease, G3 45% (8225), G2 46% (8328), and G1 9% (1672). Median duration of follow up was 57 months (2-160). Probability of death T1b at 10yrs with chemotherapy was 8.5%, and without chemotherapy was 15.1% with an absolute benefit of 6.6%. Predicted benefit in T1b using RS Clin at 10yrs was 10.8%. Probability of death for T1c at 10yrs with chemotherapy was 15.1%, and without chemotherapy was 23.5% with an absolute benefit of 8.4%. Predicted benefit in T1c using RS Clin at 10yrs was 14%. Conclusions: Patients with stage IB and IC hormone receptor positive HER2 negative breast cancers with high RS had a lower absolute benefit than predicted by RS Clin. The RSClin tool overestimated benefit of therapy in both IB and IC stages requiring caution when using this tool in patients with the lowest clinicopathologic risks.